Permitted daily exposure for diisopropyl ether as a residual solvent in pharmaceuticals

Solvents can be used in the manufacture of medicinal products provided their residual levels in the final product comply with the acceptable limits based on safety data. At worldwide level, these limits are set by the "Guideline Q3C (R6) on impurities: guideline for residual solvents" issued by the ICH. Diisopropyl ether (DIPE) is a widely used solvent but the possibility of using it in the pharmaceutical manufacture is uncertain because the ICH Q3C guideline includes it in the group of solvents for which "no adequate toxicological data on which to base a Permitted Daily Exposure (PDE) was found". We performed a risk assessment of DIPE based on available toxicological data, after carefully assessing their reliability using the Klimisch score approach. We found sufficiently reliable studies investigating subchronic, developmental, neurological toxicity and carcinogenicity in rats and genotoxicity in vitro. Recent studies also investigated a wide array of toxic effects of gasoline/DIPE mixtures as compared to gasoline alone, thus allowing identifying the effects of DIPE itself. These data allowed a comprehensive toxicological evaluation of DIPE. The main target organs of DIPE toxicity were liver and kidney. DIPE was not teratogen and had no genotoxic effects, either in vitro or in vivo. However, it appeared to increase the number of malignant tumors in rats. Therefore, DIPE could be considered as a non-genotoxic animal carcinogen and a PDE of 0.98 mg/day was calculated based on the lowest No Observed Effect Level (NOEL) value of 356 mg/m3 (corresponding to 49 mg/kg/day) for maternal toxicity in developmental rat toxicity study. In a worst-case scenario, using an exceedingly high daily dose of 10 g/day, allowed DIPE concentration in pharmaceutical substances would be 98 ppm, which is in the range of concentration limits for ICH Q3C guideline class 2 solvents. This result might be considered for regulatory decisions

Biodegradation and degradation pathway of diisopropyl ether by Mycolicibacterium sp. strain CH28

A diisopropyl ether (DIPE) degrader bacterium, Mycolicibacterium sp. strain CH28 was isolated from a pharmaceutical groundwater. Based on our results strain CH28 is capable of the complete mineralization of DIPE with a maximum degradation rate of 1.63 ± 0.03 nmol min-1 mg biomass-1 . We proposed the metabolic pathway of microbial DIPE degradation in our isolate based on the detection of 2-propanol, acetone, and acetate as degradation intermediates. Our results revealed that strain CH28 holds great potential in the bioremediation of sites contaminated with fuel oxygenate ethers (e.g.: DIPE)

The thermodynamics, mechanism and kinetics of the catalytic conversion of propylene and water to diisopropyl ether over amberlyst 15

Bibliography: leaves 297-313.Diisopropyl ether (DIPE) was synthesised in a single step from a feed of propylene and water over Amberlyst 15 ion exchange resin catalyst. It was produced in a trickle bed reactor at pressures between 1 bar and 60 bar, at temperatures between 70°C and 160°C and at overall propylene to water ratios between 1:5 and 10:1. Reaction proceeded in the liquid phase within the catalyst particles. The only reactions that occurred in the system were the hydration of propylene to form isopropanol (IPA) , the alkylation of IPA with propylene to form DIPE and the bimolecular dehydration of IP A to form DIPE and water. No side reactions such as propylene oligomerisation were observed. Starting from a feed of propylene and water the primary reaction product was IPA. IPA was subsequently consumed in two secondary reactions which produced DIPE. DIPE was produced either by the alkylation of IPA with propylene or by the bimolecular dehydration of IPA. It was generally not possible to study the two DIPE formation reactions separately as they are linked via the propylene hydration reaction. All experimental data was thus reported in terms of a hydration rate and an etherification rate, the latter being the sum of the IPA alkylation and the bimolecular IPA dehydration rates

Evaluation of Fuel Oxygenate Degradation in the Vadose Zone

Groundwater contamination by petroleum products poses a potential human health and safety risk. Methyl tert-butyl ether (MTBE) was a commonly used fuel oxygenate that was added to gasoline to meet environmental regulations. The widespread use of MTBE resulted in significant contamination of drinking water supplies across the United States. This research evaluated the degradation characteristics of potential alternative fuel oxygenates in the vadose zone. One fuel oxygenate being considered as an alternative to MTBE is diisopropyl ether (DIPE). Specifically, this thesis sought to answer three research questions: what is the potential for DIPE degradation in soil without prior microbial augmentation, how does the presence of co-contaminants, such as ethanol and toluene, impact the biodegradation of DIPE, and will the increased use of DIPE represent a potential environmental risk? Previous research related to fuel oxygenates has focused primarily on oxygenates currently used, such as MTBE and ethanol. This research focused on a potential alternative to MTBE prior to its widespread implementation and use. An experiment was run for 30 days to assess degradation characteristics for DIPE, ethanol, and toluene in the vadose zone. Due to the short length of the experiment it is not possible to determine if DIPE degradation occurred

Double Pomeron Exchange: from the ISR to the LHC

I discuss Double Pomeron Exchange processes from their first observation at the CERN Intersecting Storage Rings, focusing on glueball searches, through the observations of exclusive chi_c, photon-photon, and di-jets at the Tevatron, to prospects at the LHC for exclusive Higgs boson production.Comment: 5 pages, no figures, talk at Diffraction 2010, Otranto, Italy (September 2010

Double Pomeron Physics at the LHC

I discuss central exclusive production, otherwise known as Double Pomeron Exchange, DPE, from the ISR through the Tevatron to the LHC. There I emphasize the interest of exclusive Higgs and WW/ZZ production.Comment: Contribution to DIS05. 6 pages, no fig

QCD and Hard Diffraction at the LHC

As an introduction to QCD at the LHC I give an overview of QCD at the Tevatron, emphasizing the high Q^2 frontier which will be taken over by the LHC. After describing briefly the LHC detectors I discuss high mass diffraction, in particular central exclusive production of Higgs and vector boson pairs. I introduce the FP420 project to measure the scattered protons 420m downstream of ATLAS and CMS.Comment: To be published in Proceedings of the XIth International Conference on Elastic and Diffractive Scattering, BLois (2005). 6 pages, 0 figure

The future obligations of "project manager" as construction integral director (DIPE) in the law of buildings construction in spain (LOE)

In the year 1999 approves the Law of Construction Building (LOE, in Spanish) to regulate a sector such as construction, which contained some shortcomings from the legal point of view. Currently, the LOE has been in force 12 years, changing the spanish world of the construction, due to influenced by internationalization. Within the LOE, there regulating the different actors involved in the construction building, as the Projects design, the Director of Construction, the developer, The builder, Director of execution of the construction (actor only in Spain, similar as construcion engineer and abroad in), control entities and the users, but lacks figure Project manager will assume the delegation of the promoter helping and you organize, direct and management the process. This figure assumes that the market and contracts are not legally regulated in Spain, then should define and establish its regulation in the LOE. (Spain Construction Law) The translation in spanish of the words "Project Manager is owed to Professor Rafael de Heredia in his book Integrated Project Management, as agent acting on behalf of the organization and promoter assuming control of the project, ie Integraded Project Management . Already exist in Spain, AEDIP (Spanish Association Integrated of Project Construction management) which comprises the major companies in “Project Management” in Spain, and MeDIP (Master in Integrated Construction Project) the largest and most advanced studies at the Polytechnic University of Madrid, in "Construction Project Management" they teach which is also in Argentina. The Integrated Project ("Project Management") applied to the construction process is a methodological technique that helps to organize, control and manage the resources of the promoters in the building process. When resources are limited (which is usually most situations) to manage them efficiently becomes very important. Well, we find that in this situation, the resources are not only limited, but it is limited, so a comprehensive control and monitoring of them becomes not only important if not crucial. The alternative of starting from scratch with a team that specializes in developing these follow directly intervening to ensure that scarce resources are used in the best possible way requires the use of a specific methodology (Manual DIP, Matrix Foreign EDR breakdown structure EDP Project, Risk Management and Control, Design Management, et ..), that is the methodology used by "Projects managers" to ensure that the initial objectives of the promoters or investors are met and all actors in process, from design to construction company have the mind aim of the project will do, trying to get their interests do not prevail over the interests of the project. Among the agents listed in the building process, "Project Management" or DIPE (Director Comprehensive building process, a proposed name for possible incorporation into the LOE, ) currently not listed as such in the LOE (Act on Construction Planning ), one of the agents that exist within the building process is not regulated from the legal point of view, no obligations, ie, as is required by law to have a project, a builder, a construction management, etc. DIPE only one who wants to hire you as have been advanced knowledge of their services by the clients they have been hiring these agents, there being no legal obligation as mentioned above, then the market is dictating its ruling on this new figure, as if it were necessary, he was not hired and eventually disappeared from the building process. As the aim of this article is regular the process and implement the name of DIPE in the Spanish Law of buildings construction (LOE

Bile acids: Lipase-catalyzed synthesis of new hyodeoxycholic acid derivatives

In this work we present an efficient, environmentally friendly approach to the synthesis of a series of hyodeoxycholic acid derivatives applying Biocatalysis. Fifteen acetyl and ester derivatives, twelve of them new, were obtained through an enzymatic strategy in a fully regioselective way and in very good to excellent yield. In order to find the optimal reaction conditions, the influence of several parameters such as enzyme source, alcohol or acylating agent:substrate ratio, enzyme:substrate ratio, temperature and reaction solvent was considered. The excellent results obtained made this procedure very efficient, particularly considering the low amount of enzyme required. In addition, this methodology uses mild reaction conditions and has reduced environmental impact, making biocatalysis a suitable way to obtaining these bile acids derivatives.Fil: Chanquia, Santiago Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Ripani, Erika Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Baldessari, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Garcia Liñares, Guadalupe Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentin